Iron transport and iron regulated proteins have been found to be associated with virulence of Shigella as well as other bacterial pathogens. An additional factor associated with virulence of Shigella species is correlated with the ability of these pathogens to bind the dye Congo red. Studies proposed for this granting period are designed to answer the following questions related to iron transport and virulence: 1) How are the genes for iron transport systems organized and regulated in Shigella species; 2) What is the molecular basis for binding of Congo red dye by virulent Shigella; and 3) Are there homologous DNA sequences which confer invasiveness in virulent Congo red binding species? Experimental approaches will utilize current recombinant DNA technology to clone and characterize genes of interest. Additionally, specific biochemical and molecular biological techniques have been developed to facilitate the study of extrachromosomal elements which appear to play a important role in both gene regulation and virulence of Shigella. Studies of iron transport and virulence at the molecular level will allow us to define the role of these factors in host-bacterial interactions. Characterization of the unique regulatory mechanism(s) associated with these factors will provide basic information on the control of gene expression.